**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THE GROWING WORLD POPULATION AND ANTICIPATED FOOD SHORTAGE OVER THE NEXT SEVERAL DECADES DEMANDS ENHANCED FOOD PRODUCTION. AS PORK IS THE MOST CONSUMED MEAT GLOBALLY, INCREASED PORK PRODUCTION IS A POTENTIAL SOLUTION TO THESE CHALLENGES. INDEED, INCREASING AVERAGE LITTER SIZE BY JUST 2% WOULD YIELD 2.7 MILLION MORE PIGLETS, PROVIDING AN ECONOMIC BENEFIT BEYOND $241 MILLION TO THE SWINE INDUSTRY. HOWEVER, WHILE IMPROVED REPRODUCTIVE SUCCESS IS AMONG THE MOST EFFECTIVE APPROACHES TO ACHIEVING GREATER PRODUCTION CAPACITY, REPRODUCTIVE FAILURE STILL PRESENTS A MAJOR LIMITATION TO THE SWINE INDUSTRY. THUS, A CRITICAL NEED EXISTS FOR ENHANCED REPRODUCTIVE EFFICIENCY IN SWINE BY DEVELOPING NOVEL STRATEGIES THAT MITIGATE SWINE INFERTILITY.IN MAMMALS, REGULATION OF REPRODUCTION NORMALLY OCCURS VIA THE INTERACTION OF GNRH-I WITH ITS RECEPTOR (GNRHR-I) IN THE BRAIN, STIMULATING THE RELEASE OF THE GONADOTROPINS, LUTEINIZING HORMONE (LH) AND FOLLICLE STIMULATING HORMONE (FSH). IN FEMALES, LH AND FSH BINDING THEIR RESPECTIVE RECEPTORS ON THECA AND GRANULOSA CELLS WITHIN THE OVARY ELICIT SECRETION OF 17SS-ESTRADIOLFROM FOLLICLES. HOWEVER, THERE EXISTS A SECOND MAMMALIAN FORM OF GNRH (GNRH-II), ALONG WITH ITS COGNATE RECEPTOR (GNRHR-II), WHICH ARE EXPRESSED THROUGHOUT THE BODY. ALTHOUGH THE GENES FOR GNRH-II AND GNRHR-II ARE PRESENT IN OVER 80 MAMMALS, MOST POSSESS CODING ERRORS FOR ONE OR BOTH GENES. INTERESTINGLY, PIGS ARE THE ONLY LIVESTOCK SPECIES ENCODING A FUNCTIONAL PROTEIN FOR BOTH GNRH-II AND ITS RECEPTOR.IN FEMALES, GNRH-II AND GNRHR-II HAVE BEEN IMPLICATED IN NUTRITIONAL REGULATION OF SEXUAL BEHAVIOR, PLACENTAL FUNCTION, IMPLANTATIONAND STEROIDOGENESIS. WITH REGARD TO THE OVARY, GNRH-II AND/OR GNRHR-II HAVE BEEN DETECTED IN LUTEINIZED (THECA-LUTEAL AND GRANULOSA-LUTEAL), OVARIANSURFACE EPITHELIAL, AND OVARIAN CANCER CELLS. INDEED, ONLY ONE REPORT HAS DEMONSTRATED GNRH-II PROTEIN EXPRESSION IN THECA AND GRANULOSA CELLS OF THE PREOVULATORY FOLLICLE. YET, THESE STUDIES HAVE BEEN LIMITED TO HUMANS, PRIMATES, AND RODENTS. EXCITINGLY THOUGH, PRELIMINARY DATA FROM OUR LAB DEMONSTRATED ELEVATED CONCENTRATIONS OF GNRH-II WITHIN FOLLICULAR FLUID,AND PROTEIN LEVELS OF GNRHR-II IN BOTH THECA AND GRANULOSA CELLS OF THE PORCINE PREOVULATORY FOLLICLE. HOWEVER, THERE IS STILL A GAP IN OUR KNOWLEDGE REGARDING HOW GNRH-II AND ITS RECEPTOR INTERACT TO MEDIATE REPRODUCTIVE PROCESSES WITHIN PREOVULATORY FOLLICLES.OUR LABORATORY IS UNIQUELY POSITIONED TO EXAMINE THE ROLE OF GNRH-II AND ITS RECEPTOR IN FEMALE PIGS BECAUSE WE HAVE CREATED A TRANSGENIC LINE OF SWINE WITH REDUCED, OR KNOCKED-DOWN (KD), ENDOGENOUS LEVELS OF GNRHR-II (GNRHR-II KD). ACCORDINGLY, USING THIS TRANSGENIC LINE OF SWINE, WE SEEK TO: 1)ELUCIDATE THE ROLE OF GNRH-II AND ITS RECEPTOR IN 17SS-ESTRADIOL PRODUCTION BY GRANULOSA AND THECA CELLS OF THE PORCINE ANTRAL FOLLICLE, AND 2)DETERMINE HOW GNRH-II AND ITS RECEPTOR CONTRIBUTE TO OVULATION. AS A RESULT OFTHE PROPOSED STUDIES, WE EXPECT TO SEE A,CHANGE IN KNOWLEDGE REGARDING MECHANISMS ASSOCIATED WITH STEROIDOGENESIS IN THE PORCINE OVARY, AND SUBSEQUENT OVULATION RATES, CULMINATING IN THE DEVELOPMENT OF INNOVATIVE METHODS TO ENHANCE FERTILITY AND IDENTIFY FEMALE PIGS PREDISPOSED TO REDUCED LITTER SIZES. ULTIMATELY, THESE NEW TECHNOLOGIES WILL ALLOW FOR IMPROVED REPRODUCTIVE EFFICIENCY AND INCREASED PROFITABILITY FOR THE SWINE INDUSTRY.

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